Endoplasmic reticulum stress is a protective cellular response triggered by ER dysfunction. The ER is responsible for protein synthesis, folding, and calcium storage. Accumulation of unfolded/misfolded proteins activates the unfolded protein response (UPR). UPR signaling via transmembrane sensors (IRE1, PERK, ATF6) temporarily inhibits protein translation, upregulates chaperones to aid folding, and enhances degradation of faulty proteins. Prolonged unresolved stress leads to apoptosis. ER stress is implicated in neurodegenerative diseases, diabetes, and cancer, making its regulatory mechanisms a key focus in therapeutic research.